Atomic Orbitals, Molecular Orbitals, and Bonding
In a simplistic view, atomic orbitals are the domain of electrons orbiting around the nucleolus of atoms. Atomic orbitals and the bonds between them comprise the basis for the grand majority of chemical compounds. Pluralities of bonded atoms form molecules, and the bonds among orbitals create opportunities for molecular-scale orbitals. In many kinds of these an electron is no longer bound to a single atom but (in the viewpoint of quantum chemistry) is probabilistically shared among two or more atoms in the molecule. In some cases, molecular orbital configurations allow an electron to be shared by most or all of the atoms in the molecule.
FIG. 1, adapted from FIG. 3.12 of [1], depicts some important types of molecular orbitals as can be formed from p-orbitals of constituent atoms and that are of relevance to chemical reactions. These include the π-bond (important in the sharing of electrons among atoms for example in aromatic compounds), Walsh (“banana”) bonds (important in strained molecules such as small heterocycles), and σ-bonds (which often form the skeletan of many organic compounds and are also at times unusual players in various types chemical reactions).
For an electron to reside in a particular molecular orbital it must have, but the dictates of quantum mechanics, a particular associated energy. Quantum effects prevent more than one electron in an electron system from having the same state. State includes the spin of the electron, and the binary nature of spin results in many electrons sharing the same basic orbital situation in either pairs or individually. FIG. 2, adapted from FIG. 3.13 of [1], depicts a representative diagram of typical molecular orbital energy levels, the energy increasing as an electron migrates vertically within this hierarchy. In the ground (lowest energy), the electrons pile into the molecular orbitals with the lowest available energy state, and thus occupy the lowest possible portions of this hierarchy.
Usually to have a chemical reaction, bonds are broken, made, or both (albeit sometimes they are arguably shuffled). A new bond requires an energy to form, and breaking a bond requires energy to free an electron from its bond so that it is free to have a different future. The energy used to form and break bonds can be provided thermally, but also can be delivered photochemically, electrochemically, and by other means such as cavation processes in sonochemistry. Energy is proportional to photon frequency and thus inversely proportional to photon wavelength. Thus a plot of photon energy versus wavelength is a “y=C/x” hyperbolic curve. Since points on such a curve relate energy to wavelength, by associating bond energies to the corresponding energy point on the curve, the maximum wavelength for the bond can be graphically identified. FIG. 3 depicts the energy of various types of bounds between example elemental atoms and wavelengths required to break various bonds. Visible light lies in the range of 500-700 nm, with wavelengths less than 500 nm forming the ultraviolet and wavelengths less than ˜250 nm forming the “far ultraviolet.”
High-power LEDs are available in the visible spectrum and at ultraviolet wavelengths. Recently “far ultraviolet” LEDs have also become commercially available, for example including those going down to 240 nm or below (such as those available from Sensor Electronic Technology, Inc., 1195 Atlas Road, Columbia, S.C., 29209, 803-647-9757. On the other side of the visible light range, infrared LEDs are commercially available that go to wavelengths as long as 2400 nm, for example those available from Laser 2000 GMbH, Argelsrieder Feld 14, D-82234, Wessling, FRG, +49-8153-405-0. Thus the curve depicted in FIG. 3 is useful for relating photochemical synthesis opportunities to commercially available visible light LEDs, ultraviolet LEDs, far-ultraviolet LEDs, and infrared LEDs. Except for triple bonds and carbon-oxygen bonds, a very large number of bond energies are within the reach of photostimulation by commercially available LEDs. Further these LEDs are physically very small, consume low power, and are readily installed in a wide range of physical arrangements. Thus, in an inventive step provided for by the invention, the resulting situation is thus well suited for microfluidics and lab-on-a-chip environments performing chemical synthesis, and the very-to-extremely small physical scale of such devices allow the delivery of high photon fluxes to small volumes of liquids, gases, and solids in various situations. Further, LEDs also behave as wavelength-selective photodiodes. Thus, in an inventive step provided for by the invention, LEDs can be adapted for use as light sensors, albeit with special electronics for working with photovoltages, photocurrents, photo-induced space-charge effects, and non-bandpass aspects of LED sensitivity with respect to incident light wavelength. The invention thus further provides microfluidics and lab-on-a-chip environments with capabilities for photochemical and photophysics analysis
In many circumstances energy, as well as electrons (as useful for electron-transfer reactions and umpoled reactions) can be provided by electrodes immersed in various types of materials and solvents (including non-aqueous solvents). In an inventive step provided for my the invention, such electrodes can be rendered in very small physical size for use in microfluidics and lab-on-a-chip environments, and thus the invention further provides microfluidics and lab-on-a-chip environments with electrochemical synthesis and analysis.
Further, photochemical and electrochemical processes generate excited states and reactive intermediates. The invention leverages these to further provide for excited states and reactive intermediates to be used in sequence or combination for chemical synthesis, analysis, or both. Additionally, the currency of excited states and reactive intermediates can, in another aspect of the invention, be put into a framework for synthon chemistry, anion relay chemistry, complex and coordination chemistry, supramolecular chemistry, confined and organized media chemistry.
In order to provide a foundation for the invention, attention is directed to some additional fundamentals that have been gathered together from a variety of areas and brought to use in various aspects of the present invention.
High-Level Overview of Chemical Reaction Initiation-Energy Processes
Many types of chemical reactions occur as a result of combining chemicals in ambient thermal and pressure conditions. Because these combinations occur under ambient conditions without additional excitation, for the purposes of this discussion these reactions can be termed ambient chemical reactions. Typically the chemical species in ambient chemical reactions are in ground-state rather than in an excited state.
Other chemical reactions require the addition of energy so that at least some reactants attain an activation energy required for the reaction to occur. In most laboratory and commercial production of chemicals, activation energy is attained by adding heat. Because these occur under thermally-induced conditions, for the purposes of this discussion these reactions can be termed thermochemical reactions.
Other types of chemical reaction processes obtain activation energy by other means. When light is used as the reaction-inducing energy source, the resultant reactions can be termed photochemical reactions. When an electrical current is used as the reaction-inducing energy source, the resultant reactions can be termed electrochemical reactions. When vibrations are used (invoke extremely high-energy cavation processes, for example) the resultant reactions can be termed sonochemical reactions. There are also other lesser known as well as largely unexplored possible variations and relatives of these, for example use of one or more of microwave excitation, electric fields, and or magnetic fields to induce chemical reactions.
Photochemical Reaction Processes
Photochemistry comprises a wide range of processes and phenomena, but in particular includes photochemical reaction processes wherein one photon (or more in high-intensity situations) is absorbed either:                directly by a reactant, or        indirectly by a photosensitizer (for example as tetraphenylporphyrin, cadmium, xenon, zinc, benzophenone, and organic dyes such as methylene blue) associated with and transferring absorbed energy to a reactant,and as a result elevating the energy of the reactant to an excited state which subsequently permits or causes a chemical reaction. The first-level excited states associated with photochemistry and most photophysics typically have lower energy than the energy required for breaking a bound, so the LEDs described earlier in conjunction with FIG. 3 are typically sufficient to create at least first-level excited states in atoms, ions, molecules, complexes, and supramolecular structures.        
For some photochemical reactions, the necessary activation energy is obtained (directly or indirectly) by the absorption of light. For other photochemical reactions, the resultant added energy obtained by the absorption of light (directly or indirectly) changes the electron configuration of a molecule, resulting in the opening of a normally unavailable reaction pathway.
Examples of photochemical reactions include electron transfer reactions, pericyclic/electrocyclic reactions, photoisomerization reactions, type I (photochemical cleavage) and type II Norrish reactions of atmospheric science, and an extremely wide variety of other reactions. For example, just in the context of photochemistry within transition metal complexes at least the following varieties of reaction types are known:                Photoaddition        Photocycloaddition        Photo-induced rearrangements        Photoisomerization        Photoreduction        Photodimerization        Photoassisted double-bond migration        Photo-induced insertion        Photochemical ion ring-opening        Photopolymerization        Photosubstitution and photoreplacement        Photohydrogenation        Photodehydrogenation and photo-induced dehydrogenation        Photo-oxygenation        Photooxidation        Photoassisted carbonylation        PhotodecarboxylationOutside the world of metal complexes, each of these photochemical processes can also be found, along with other common photochemical processes (for example photoabstraction) and other more specialized photochemical processes (such as photopinacolization).        
Overall, photochemical reactions offer a rich, useful, rapidly evolving, and increasingly appreciated chemistry with many advantages and differences over ground-state chemistry, as well as (as shown in the list above) many things in common. Of particular note are the following:                Photochemical reactions provide a means to produce some compounds that cannot be readily or realistically obtained by ambient or thermochemical reactions. In some cases of this, it is the unusual electron configurations that provide the pathway. In other cases, the fact that heating typically involves the simultaneous heating of multiple reactants and reaction products at once, some of which can thermally decompose or otherwise not remain stably available for the desired reaction.        Excited state molecules and atoms behave as better electron donors and better electron acceptors than ground-state state molecules and atoms. Additionally, excited states have very different redox properties than those associated with ground-states. Both of these facts are useful in reaction and chemical synthesis planning.        Many photochemical reactions involve the production of reactive intermediates. Although a diverse filed in itself, and one of value to aspects the invention, a definition for reactive intermediates suitable for this discussion can be found in [6] (which also provides the more formal IUPAC Gold Book definition):                    “A reaction intermediate or an intermediate is a molecular entity that is formed from the reactants (or preceding intermediates) and reacts further to give the directly observed products of a chemical reaction. Most chemical reactions are stepwise, that is they take more than one elementary step to complete. An intermediate is the reaction product of each of these steps, except for the last one, which forms the final product. Reactive intermediates are usually short lived and are very seldom isolated. Also, owing to the short lifetime, they do not remain in the product mixture.”                         In many photochemical reactions the chemical steps following photoexcitation are often that of radical ion reactive intermediates, chemistry not typically observed in ground-state organic reactions.        
Photochemical reactions typically are extremely fast, for example in the nanosecond to even femtoseconds range, and in general many orders of magnitude faster than thermochemical reactions.
Examples of reactive intermediates of relevance to the invention include but are not limited to:                Arynes        Carbenes        Carbenoids        Carbocations        Carbanions (including ylides which in circumstances can be adapted to serve as reagents, for example as used in Wittig reactions)        Carbynes        Free radicals        Nitrenes        Nitrenium (a.k.a. aminylim and imidonium) ions        Ketenes (in some views)        
Some reactive intermediates can be stabilized; examples of these include but are not limited to:                Oxonium ions (stabilized equivalents of carbocations)        Enolates (stabilized equivalents of carbanions)        Ylides (see above)        Ynolates (in the sense that they can serve as ketene precursors relevant to synthons, to be discussed).        
It is noted that reactive intermediates can be chemically trapped by various means, including for example trapping of photochemically-generated reactive intermediates via amines. Such chemical trapping typically has been done for the purposes of verifying the existence and type of reactive intermediates. Additionally, reactive intermediates can be chemically stabilized (for example, as in the case of enolates). Trapped or chemically stabilized reactive intermediates can be freed and restored for use in later reactions.
Additionally, reactive species and photosensitizers have a range of absorption spectral peaks and valleys that differ so profoundly that they can readily form the basis of contemporary identification of substances.
Photochemistry has yet additional synthesis power and capabilities besides serving as a replacement for heat as a energy source for initiating chemical reactions. The excited states move electrons into higher orbitals and thus change aspects of the geometry in which electrons and orbitals interact and intermesh. A telling example of this is the case of pericyclic reactions wherein the set of all possible reactions in most cases split mutually-exclusively as to which reactions can occur with thermal excitation (i.e., in ground states) and which can occur with photochemical or other excitations that produces excited states. By way of orientation FIG. 4 depicts a simplified non-comprehensive view of the collection of chemical reactions calling out concerted reactions, percyclic reactions, multi-step reactions, and reactive intermediates. In studying these, frontier orbital theory is often used to replace complicated Born-Oppenheimer calculations with geometric structures relationships. One of the concepts used is the geometric notion of conrotary and disrotary action in positioning atoms for particular bonding circumstances. FIG. 5a, adapted from FIG. 2.43 of [10], depicts an exemplary conrotary action as can occur in a chemical reaction while FIG. 5b, adapted from FIG. 2.44 of [10], depicts an exemplary disrotary action as can occur in a chemical reaction. Another concept is the notion of supra- and antara-facial shapes of molecular orbitals. The Woodman-Hoffman rules (whose original creation was surprisingly claimed by Corey of synthon frame late in his career) predict the outcomes of ground-state and excited-state situations with respect to conrotary/disrotary actions, supra- and antara-facial shapes of molecular orbitals, and related concepts.
FIG. 6, partially adapted from [11] and further augmented, depicts a tabular summary of representative exemplary aspects of the Woodward-Hoffman rules for pericyclic chemical reactions. The complementary structure of the partition between reactions that are allowed or disallowed for ground-state and excited-state constituents is seen vividly in this table. (It is noted however, that in some circumstance steric effects may interfere with the predictions comprised by the table.) FIG. 7 combines parts of FIG. 4 and information from the table of FIG. 6 to demonstrate an example mutually-exclusive partition of possible pericyclic reactions into those reactions that are only possible with constituents excited states (as produced by photon absorption, and hence as occur in photochemical reactions) and those reactions that are only possible with constituents in ground states (as occur in thermal reactions).
Electrochemical Reaction Processes
Electrochemistry has historically held a significantly different role in the landscape of chemistry. Recent developments in organic electrochemistry have revealed or provided techniques for the following aspects relevant to the present invention:                The ability of electrochemical processes to add and remove electrons from organic molecules;        As a result, electrochemical processes can be used to reverse the polarity of functional groups (i.e., change nucleophiles into electrophiles and electrophiles into nucleophiles), which in turn can be employed to trigger umpolung (a.k.a. polarity inversion, polarity reversal) reactions not unlike those applied in Grignard reactions and condensations of aromatic aldehyde;        Reactive intermediates can be created;        The reactive intermediates can be trapped;        The trapped reactive intermediates can be employed to couple like-polarity functional groups (i.e., two nucleophiles or two electrophiles) in ways otherwise not thought to be possible;        These permit the creation of potential new synthesis approaches for complex molecules.        
A slight older development in electrochemistry yet with a contemporarily life is that of electrochemical-induced chemiluminescence (“ECL”). The formal area of electrochemical-induced chemiluminescence has its own themes, orientations, motivations and applications, but in the course of these demonstrates the generation of excited states via electrochemical processes, for example the “Twisted Internal Charge Transfer” state (‘TITC’).
“Photoelectrochemistry” and “Electrophotochemistry”
It is noted that the terms “photoelectrochemistry” and “electrophotochemistry” have repeatedly emerged in the context of describing various situations such as:                electrochemical processes and photochemical processes working together either synergistically (for example improving photocatalytic efficiency) or in rapid sequence (electrochemical generation of agents followed by photochemical generation of active radicals);        combining photochemical and electrochemical methods for study of the oxidation-reduction, excited states, or reactive intermediates;        chemistry resulting from the interaction of light with electrochemical processes;        solar cells for generating electrical energy from light by means of a semiconducting photoanode and a metal cathode immersed in an electrolyte;        types of electrochemical luminescence.Sonochemical Reaction Processes        
Sonochemical processes have also been shown to generate excited states and reactive intermediates via the extreme thermal conditions occurring at cavitation sites, and sonochemical technology has been shown to be miniaturized to a microfluidic scale, but due to the mechanical power and acoustic transmission within materials, isolation is at least complex (if not impractical for low-cost mass-produced implementation). It is noted that there are results suggesting sonification can aid and influence photochemical reaction processes via reactant micromixing and shockwaves. It is also noted that there are results suggesting ultrasonic stimulation can aid and influence electrochemical reaction processes.
Synthon Retrosynthesis Techniques
Synthon retrosynthetic techniques can be used to formalize chemical synthesis. FIG. 8, adapted from [16], depicts a representational example of retrosynthetic analysis. Various decompositions of the desired product molecule are considered, and for each candidate considered pathways are selected. The pathway alternatives comprise, for example, alternative assignments of opposing charges to the constituents. From these synthod primitives reagents can be selected. Although still evolving, synthon-based chemical synthesis is attractive for a wide-range chemical processing system under computer control (as provided for by selected aspects of the invention). Even though the synthon abstractions and the reagents that represent them are readily mappable to a computer and algorithmic representation, work in this area to date is limited. However because the synthon abstractions and the reagents that represent them are readily mappable to a computer and algorithmic representation, the invention provides for computer-processor control of synthon analysis and chemical synthesis design.